For example, the multi-billion dollar pharmaceutical sleep aid market targets primarily classical neurotransmitters such as norepinephrine and, in particular, GABA. Neuropeptides are protein-based neurotransmitters of particular interest as potential targets of drug treatments due to their diversity and selectivity. Among these are several neuropeptides, such as short neuropeptide F (sNPF), pigment-dispersing factor (PDF), neuropeptide F (NPF), SIFamide, myoinhibitory peptide (MIP), CCHa1, allatostatin-A, and ion transport peptide (ITP). At the molecular level, many genes and neurotransmitters have been linked to sleep control in the fly. In terms of neural circuits, we have learned that sleep in Drosophila is regulated by multiple brain regions, including circadian clock neurons, the mushroom bodies, the pars intercerebralis, the ellipsoid body, and the fan-shaped body. Additionally, sleep deprivation in Drosophila impairs vigilance and produces a subsequent homeostatic sleep rebound. Behaviorally, sleep in Drosophila has circadian rhythmicity, is associated with a preferred posture and sleep location, and sleeping animals have an increased arousal threshold. Drosophila shares many behavioral and neurochemical characteristics of sleep with mammalian species, but has a much simpler nervous system and a vast capacity for genetic manipulations. The fruit fly Drosophila melanogaster in particular has emerged as a useful system in which to study sleep. Due to the complexity of human sleep systems, as well as their inaccessibility for experimental manipulation, studying animals with simpler nervous systems can be a powerful approach. However, the cellular and molecular mechanisms that regulate sleep are still not well understood. Sleep disturbances due to insomnia, sleep apnea, psychiatric and neurological disorders, jetlag, and shift work, and daily pressures are also highly prevalent and disruptive in today’s society. Sleep is a critical and nearly universal behavioral state in which humans spend approximately one third of their lives. Future studies will determine the specific roles of sub-populations of sNPF-producing neurons, and will also assess how sNPF neurons act in concert with other neuronal circuits to control sleep. We have also presented evidence that sNPF neuron activation produces a homeostatic sleep drive that can be dissipated at times long after the neurons were stimulated. These results provide supportive evidence that sNPF-producing neurons promote long-lasting increases in sleep, and show for the first time that even brief periods of activation of these neurons can cause changes in behavior that persist after cessation of activation. Video recording of individual fly responses to short-term (0.5–20 second) activation of sNPF neurons demonstrated a clear light duration-dependent decrease in movement during the subsequent 4-minute period. Changing the timing of red light stimulation to times of day when flies were already asleep caused the control flies to wake up (due to the pulse of light), but the flies in which sNPF neurons were activated stayed asleep through the light pulse, and then showed further increases in sleep at later points when they would have normally been waking up. We found that activating sNPF neurons for as little as 3 seconds at a time of day when most flies were awake caused a rapid transition to sleep that persisted for another 2+ hours following the stimulation. Combining sNPF-GAL4 and UAS-Chrimson transgenes allowed us to activate sNPF neurons using red light. In this study, we utilized optogenetic activation of neuronal populations expressing sNPF to determine the causal effects of precisely timed activity in these cells on sleep behavior. For example, in Drosophila melanogaster, the neuropeptide Y (NPY)-related transmitter short neuropeptide F (sNPF) appears to promote sleep. Several key signaling molecules that regulate sleep across taxa come from the family of neuropeptide transmitters. Sleep abnormalities have widespread and costly public health consequences, yet we have only a rudimentary understanding of the events occurring at the cellular level in the brain that regulate sleep.
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